HIV is a sexually transmitted disease and a vaccine capable of preventing sexual transmission of HIV should elicit mucosal immune responses in the genital tract. To see if the transient viremia and immune response that occurs after intravaginal (IVAG) inoculation SHIV 89.6 could confer protection from IVAG SIV challenge, the SHIV 89.6 infected/exposed animals were challenged intravaginally with SIVmac239. Both control animals and one animal that was exposed IVAG to SHIV (but never became viremic) became viremic after SIV239 challenge. Two of the animals that been infected with SHIV89.6 became viremic after challenge with SIV but the virus loads were very low compared to the control animals. Three of the animals that been infected with SHIV89.6 completely resisted challenge with SIV239. These 3 animals all had SIV-specific cytotoxic T cell responses in the peripheral blood at the time of challenge. This is the best protection from vaginal challenge ever seen in the SIV system. Currently detailed studies are underway to characterize the protective immune responses in these animals. *KEY*Vaccine protection, Mucosal immunity, SIV vaginal transmission